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Development of Reagents for Highly Efficient Transfection of siRNA into Immune Cells and Their Application to Cancer Immunotherapy
Development of next-generation drug delivery systems
We have developed a reagent (YSK12-MEND) to introduce siRNA into immune cells with high efficiency. If siRNA is introduced into immune cells using this reagent, the expression of immunosuppressive genes can be reduced with high efficiency, and thus it is expected to be applied to cancer immunotherapy using immune functions.
Research
We have developed YSK12-MEND, a reagent that can efficiently transfect siRNA, a gene expression inhibitor, into mouse and human immune cells. By using the novel reagent, the efficiency of siRNA transfection into mouse dendritic cells has improved more than 10-fold compared to the commercial product (Lipofectamine RNAiMAX). It is known that the function of immune cells is suppressed by cancer cells in cancer patients, although humans have an immune function to fight cancer cells. siRNA delivery using YSK12-MEND can efficiently suppress the expression of immunosuppressive genes in immune cells, which will enable humans to fight cancer cells with their own immune function. YSK12-MEND is expected to be one of the promising candidates for this purpose.
Takashi Nakamura Assistant Professor -
In Vivo Nucleic Acid Delivery System Based on the Development of Unique Functional Lipids
Balancing world-class functional delivery of nucleic acids and safety
We have developed a unique group of functional lipids for the safe and efficient in vivo delivery of siRNA. The lipid nanoparticles containing these lipids showed world-class functional delivery of siRNA in hepatocytes due to their excellent endosomal escape ability and high safety due to their biodegradability.
Research
The key to the practical application of siRNA is the development of superior delivery technology, but there is still much room for improvement in the delivery efficiency. In addition, from the viewpoint of practicality, it is also important to secure a wide safe therapeutic window. It is also highly desirable to develop platform technologies that can provide appropriate formulations for different purposes without being limited to specific applications. To achieve these goals, we have developed a unique group of pH-sensitive cationic lipids. We achieved the modulation of acid dissociation constants, which is an important factor for the pharmacokinetics of lipid nanoparticles, enabling a target-specific molecular design. The lipid nanoparticles containing the novel lipid CL4H6 induced gene silencing in hepatocytes with world-class efficiency. No significant hepatotoxicity was also observed even after the administration of approximately 3,000-fold higher dose for 50% gene silencing, thus a high level of safety was confirmed. CL4H6 was rapidly degraded and eliminated after siRNA delivery.
Yusuke Sato Associate Professor
